It is the general aim of this research program to study the basic physiological and pharmacological characteristics of the centrally, reflexly and peripherally evoked electrodermal response and to determine if this system would be a suitable model for the study of drug action on the central nervous system. An attempt will be made to define, by means of stimulation and ablation techniques, the efferent brain stem pathway(s) for eliciting electrodermal responses and those regions necessary for integration of electrodermal reflexes. Once the excitatory elements and their interrelationships are defined, direct (central and peripheral) and reflex activation of this system will be utilized as a model with which to study drug effects on the CNS. As the peripheral neuro-transmitter to the sweat glands is acetylcholine, this system would be particularly suitable for the study of those adrenergic drugs thought to have a central action as well as their known peripheral effects. Initial pharmacological studies will be concerned with elucidating the possible central efferent neurotransmitter mechanisms involved. This will be accomplished by observing the effects of conventional blocking drugs and transmitter synthesis inhibitors on simultaneously evoked central and peripheral responses. Once the basic physiological and pharmacological mechanisms have been determined, this system will be utilized in the systematic analysis of the CNS actions of selected antihypertensive and antipsychotic agents. BIBLIOGRAPHIC REFERENCES: Koss, M.C. and M.A. Davison, The electrodermal response as a model for central sympathetic reactivity: the action of clonidine, Eur. J. Pharmacol. (In press, May 1976).